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H. Paradis, E. Miskiewicz, W. V. Good, H. E. Grossniklaus, R. L. Gendron; Tubedown Suppression in Choroidal and Retinal Vasculature During Aging. Invest. Ophthalmol. Vis. Sci. 2007;48(13):40.
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During aging, vision loss is an important problem that greatly impacts upon the quality of life and the maintenance of functional autonomy. Blood vessel overgrowth contributes to retinopathy in age-related blinding eye diseases which are traumatic to patients and are major burdens to the health care system: Both diabetic retinopathy and age-related macular degeneration are the leading causes of blindness in western populations and in people over age 60, respectively. Both diseases involve either retinal and/or sub-retinal blood vessel overgrowth. New improved therapies are needed to prevent and treat age-related retinopathies. We have discovered Tubedown, a novel factor which is necessary for the maintenance of healthy retina by preventing retinal and sub-retinal blood vessel overgrowth. Moreover, diabetic patients with retinal blood vessel overgrowth show loss of Tubedown expression in retinal blood vessels. Choroidal and retinal neovascular lesions observed in a Tubedown knockdown mouse model increase in severity with prolonged length of time of suppression of Tubedown. Thus, we hypothesized that age-related loss of Tubedown expression may be a causative factor in development of age-related retinal and choroidal neovascularization.
The expression of Tubedown in retinas of young, middle aged and old mice was assessed by immunohistochemistry and western blotting. Expression of retinal and choroidal Tubedown was also evaluated by immunohistochemistry in specimens of young, middle age and old human individuals.
Aging groups of mice show an age-related loss of retinal Tubedown expression. Expression of Tubedown was significantly decreased in older specimens of human retina in both choroidal and retinal vessels.
Our work suggests that Tubedown loss in the aging retina may be an indicator and predisposing factor for age-related blinding eye diseases.
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